Skarkova Veronika, Vitovcova Barbora, Matouskova Petra, Manethova Monika, Kazimirova Petra, Skarka Adam, Brynychova Veronika, Soucek Pavel, Vosmikova Hana, Rudolf Emil
Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Zborovska 2089, 500 03 Hradec Kralove, Czech Republic.
Department of Biochemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Cancers (Basel). 2022 Oct 20;14(20):5146. doi: 10.3390/cancers14205146.
(1) Background: N-cadherin expression, epithelial-to-mesenchymal transition (EMT) and aggressive biological phenotype of tumor cells are linked although the underlying mechanisms are not entirely clear. (2) Methods: In this study, we used two different in vitro cell models with varying N-cadherin expression (stabilized lines and primocultures) and investigated their select biological features including the degree of their chemoresistance both in vitro as well as in vivo. (3) Results: We report that although enforced N-cadherin expression changes select morphological and behavioral characteristics of exposed cells, it fails to successfully reprogram cells to the aggressive, chemoresistant phenotype both in vitro as well as in vivo as verified by implantation of those cells into athymic mice. Conversely, primocultures of patient-colonic cells with naturally high levels of N-cadherin expression show fully aggressive and chemoresistant phenotype pertinent to EMT (in vitro and in vivo), with a potential to develop new mutations and in the presence of dysregulated regulatory pathways as represented by investigated miRNA profiles. (4) Conclusions: The presented results bring new facts concerning the functional axis of N-cadherin expression and related biological features of colon cancer cells and highlight colon cancer primocultures as a useful model for such studies.
(1) 背景:N-钙黏蛋白的表达、上皮-间质转化(EMT)与肿瘤细胞的侵袭性生物学表型相关,尽管其潜在机制尚不完全清楚。(2) 方法:在本研究中,我们使用了两种不同的体外细胞模型,它们的N-钙黏蛋白表达水平不同(稳定系和原代培养物),并研究了它们的一些生物学特性,包括体外和体内的化疗耐药程度。(3) 结果:我们报告称,尽管强制表达N-钙黏蛋白会改变暴露细胞的某些形态和行为特征,但将这些细胞植入无胸腺小鼠体内验证发现,它未能在体外和体内成功地将细胞重编程为具有侵袭性、化疗耐药的表型。相反,N-钙黏蛋白表达水平天然较高的患者结肠细胞原代培养物表现出与EMT相关的完全侵袭性和化疗耐药表型(体外和体内),有产生新突变的可能性,并且存在以所研究的miRNA谱为代表的失调调控途径。(4) 结论:所呈现的结果带来了关于N-钙黏蛋白表达功能轴及结肠癌细胞相关生物学特性的新事实,并突出了结肠癌细胞原代培养物作为此类研究有用模型的作用。